Karl Deisseroth wins 4 million euros Fresenius Research Prize

Karl Deisseroth, MD, PhD, a Stanford University professor of bioengineering and of psychiatry, has won the 2017 Fresenius Research Prize for his pioneering work in two distinct biomedical technologies — optogenetics and hydrogel-tissue chemistry — and for exploring his clinical specialty, depression, at the level of its underlying neural circuitry. Deisseroth, who holds the D.H. Chen Professorship and is a Howard Hughes Medical Institute investigator, accepted the award today at a ceremony in Berlin. He will also give a talk, to be followed by a symposium, on June 1.

The Fresenius Prize is presented every four years to a single scientist by the Else Kroner-Fresenius Foundation in Germany. The prize — the world’s most valuable for scientific achievement — comes with a cash award of 4 million euros ($4.47 million): 3.5 million euros for Deisseroth’s laboratory, and 500,000 euros for his personal use.

Deisseroth is only the second scientist to receive the prize, which was launched in 2013 and recognizes achievement in medical research. The 2013 recipient was Yale University immunologist Ruslan Medzhitov, PhD.

“We are proud that Karl has been recognized for his groundbreaking discoveries,” said Stanford University President Marc Tessier-Lavigne, PhD. “Application of his pioneering technologies by scientists worldwide is accelerating understanding and development of therapies for debilitating neurological and psychological diseases, and Karl’s own research has provided deep insight into circuit mechanisms of depression.

Karl’s work exemplifies how brilliant scientific research can improve lives and improve our world.”

Lloyd Minor, MD, dean of the Stanford School of Medicine, noted that Deisseroth continues to see psychiatric patients on a regular basis. “Karl speaks of the profound impact it’s had on him to know and treat patients with psychiatric disorders and to see firsthand the debilitating nature of these disorders and their effects on patients and their families,” Minor said. “His research promises to one day enable millions of people with mental illness to be treated much more effectively than they are today.”

Pioneered in Deisseroth’s lab between 2004 and 2009, optogenetics is a technology that allows scientists to precisely manipulate nerve-cell activity in freely moving animals. Genes encoding light-sensitive proteins, derived from microorganisms, are inserted into targeted nerve cells. As a result, these cells’ signaling activity can be turned on or off with the flick of a switch by a pulse of laser light, delivered through a hair-thin optical fiber that has been implanted into the animal’s brain. Scientists can deduce the role played by particular nerve cells, relays and circuits by observing the effects of these manipulations on the animal’s behavior.

Making tissue transparent

Hydrogel-tissue chemistry, developed in Deisseroth’s lab between 2009 and 2016, renders intact tissue samples — and even entire organs of small animals — both transparent to light and permeable to bulky molecular probes. It involves replacing the tissue’s fatty substances, which impede transparency, with a hydrogel matrix that not only permits the transmission of light but also permits the transit of large molecules, such as labeled antibodies or oligonucleotides, which can pinpoint the presence of particular proteins or DNA sequences on or in the tissue’s constituent cells. With the help of the sophisticated methodologies developed in his lab, Deisseroth has co-authored many papers on the underpinnings of depression. He and his team have teased apart the separate neural circuits implicated in different aspects of this multifactorial disorder, such as anhedonia (the failure to experience pleasure) versus hopelessness (the inability to rise to a challenge).

Deisseroth’s lab is now taking advantage of high-powered data-collection, data-storage and data-analysis methods that have only recently become available. “We’re starting to do whole-brain analysis, collecting information from every cell in the brain and getting insights from not leaving anything out,” he said.

It’s rare for a researcher to achieve even one breakthrough technology. The development of two such game-changers, as in Deisseroth’s case, is widely considered remarkable. Still, he said, “Our primary goal isn’t to develop new methods for their own sake, but to design techniques that help us answer the questions we want to answer. We’re just biologists.”